Nearly 70% of women experience some form of sadness, anhedonia and anxiety in the weeks following the birth of a child [1,2]. Most women eventually feel better in the weeks after birth, but approximately 10-20% of women may continue to experience postpartum depression (PPD). Suicide is one of the leading causes of death in new mothers, sadly indicating that doctors may be unable to diagnose or effectively treat PPD within the timeframe that it emerges [3,4]. The risk factors for PPD include maternal isolation, negative life events, and low socioeconomic status or employment, suggesting that when mothers don't have the resources and support that they need, they are at increased risk of developing postpartum mood disorders. Yet the exact mechanisms that precipitate these changes in mood postpartum are still unknown. It is well-known that the function of the immune and endocrine systems are significantly altered during pregnancy and postpartum [5]. There is also a dramatic change in the neuroimmune system during and just after pregnancy in female rats [6]. Female rats exhibit anhedonia, as measured by sucrose preference test, on the day of birth that is associated with an increase in Interleukin (IL)-6 expression in the brain on the day of birth [7,8]. The goal of the current experiments is to determine whether a relevant maternal stress, in the form of limited bedding and nesting, can precipitate persistent postpartum anhedonia associated with a significant change in immune molecules, stress hormones or pregnancy hormones. This proposal also seeks to determine significant changes in neural activity associated with postpartum anhedonia and deficits in maternal care. The hope is that future research models incorporate relevant environmental risk factors of PPD to better understand they impact the physiological, behavioral and neural state associated with negative postpartum mood.